The present invention relates generally to spray apparatus and methods. More particularly, the present invention pertains to multiple nozzle spray methods and apparatus, e.g., multiple nozzle electrospray methods and apparatus.
It has been recognized that microsphere production technology can produce drugs or pharmaceuticals that can be taken up by cells, e.g., cells in an intestinal or stomach wall or lining, and may cross into the bloodstream. Such uptake or absorption into the cell is determined at least in part by the surface chemistry of the microspheres. Uptake of microspheres containing macromolecules, e.g., encapsulated proteins, has also been demonstrated.
Currently in drug production, top-down processes are typically used to produce drug particles. For example, in such processes, particles may be formed using grinding techniques. Further, for example, it has been described that such particles may be formed by removing solvent from a mixture that includes the active ingredient as it is being sprayed into a stream of air, e.g., hot air drying.
Electrohydrodynamic spraying (or electrospray) has been used to produce nanoparticles from, for example, solutions or colloidal suspensions. The electrospray is capable of producing nanoparticles that are 10-100 times smaller than, for example, conventional pneumatic atomization techniques. This size of particles allows product that includes such particles to have 100-10,000 times larger surface area than those produced from the conventional techniques, for a given quantity of spray solution.
The increased surface area forms the basis of enabling technology for various important applications. For example, new chemicals being synthesized as future drug products are decreasing in aqueous solubility to such an extent as to present major delivery and development challenges. If the drug products employ nanoparticles rather than macroparticles, the increased surface area results in a significantly greater dissolution rate and/or higher solubility rate. This may allow for superior and/or even enabling drug delivery. Nanoparticle medicine may increase the bioavailability and speed up the response time of the delivered drug. Thus, nanoparticle technology has the potential to significantly impact the pharmaceutical industry.
As described in U.S. Pat. No. 6,105,571 to Coffee, entitled xe2x80x9cDispensing Device,xe2x80x9d issued Aug. 22, 2000, particles are generated that may comprise biologically active material, for example, particles may contain matter such as peptides or large biomolecules such as insulin and/or other pharmaceutical components for enabling delivery of an active component into the blood stream. As indicated therein, electrohydrodynamic processes are used to produce particles, but primarily are used to produce fibres or fibre fragments.
One limiting factor in employing electrospray or electrohydrodynamic techniques for particle generation is that generally only a single spray-nozzle dispenser is used that can deliver only a small quantity of solution, e.g., a few xcexcl/min. A major challenge and problem is the inability to increase the mass throughput from such an electrospray device that can produce nanoparticles so that electrohydrodynamic techniques can be used to deliver industrial quantities particles for use in various products.
U.S. Pat. No. 6,105,571 cited above, shows use of multiple nozzles to produce fibres or particles as described therein. However, problems associated with multiple nozzle approaches are not addressed, e.g., the space charge effect of particles produced using electrospray techniques, arcing between nozzles, etc.
For the above reasons, there is a need in the art for mass throughput apparatus and methods which overcome the problems described above, and other problems as will become apparent to one skilled in the art from the detailed description below. The present invention provides apparatus and methods that produce nanoparticles with high mass throughput, e.g., can produce large quantities of nanoparticles for use in various applications, e.g., pharmaceutical, biological material production for gene therapy, coatings, fabrication processes, etc.
An electrospraying method of the present invention may include one or more of the following features: providing a plurality of nozzle structures, wherein each nozzle structure includes at least one opening defined along a center axis of the nozzle structure and terminating at a dispensing end thereof from which a spray of particles having an electrical charge applied thereto is dispensed; nozzle structures that are separated from adjacent nozzle structures by at least an internozzle distance (L) defined by the distance between center axes of the nozzle structures, wherein the ratio of the internozzle distance (L) to a diameter (D) of the opening at the dispensing end is equal to or greater than 2; dispensing a spray of particles from each of a plurality of nozzle structures by creating a nonuniform electrical field between the dispensing ends from which the sprays are established and an electrode electrically isolated from the dispensing ends; nozzle structures that include a capillary tube comprised of a body portion and a tapered capillary tip at the dispensing end of the capillary tube; nozzle structures that include a tapered portion used to define an opening, wherein at least a part of each of the nozzle structures extends from an integral multiple nozzle structure conductive portion; nozzle structures that include a solid post along a center axis extending through an opening at a dispensing end thereof; dispensing ends of the nozzle structures that are positioned in an x-y plane and have the center axis thereof aligned along the z axis; dispensing a spray of microdroplets including an active ingredient, wherein the electrical charge is concentrated on the active ingredient as the microdroplet evaporates; providing a circular configuration of nozzle structures including an outer multiple nozzle structure ring and one or more inner multiple nozzle structure rings, wherein each of the outer multiple nozzle structure ring and the inner multiple nozzle structure rings are concentric about a center nozzle structure; providing a circular configuration of nozzle structures, wherein each of the nozzle structures of the one or more inner multiple nozzle structure rings are at a substantially equal internozzle distance (L) from adjacent nozzle structures; isolating the dispensing ends of the nozzle structures from one another using separation structures such that a cone jet is allowed to form at the dispensing end of each nozzle structure; dispensing particles that have a nominal diameter of about 1 nanometers to about 2000 nanometers; providing nozzle structures that include at least a first and second opening terminating at the dispensing end of each nozzle structure; providing flows of fluid compositions at the first opening and second opening and establishing a spray of particles from such fluid compositions (e.g., a first fluid composition including an active ingredient and a second fluid composition including a coating component); providing an excipient material and combining the spray of particles with the excipient material; providing a charged pattern and collecting the spray of particles on the charged pattern; dispensing the spray of particles into a container operable for inhalation by a user; and dispensing the spray of particles at a rate in the range of 2 grams/minute to 50 grams/minute.
An apparatus for electrospraying particles according to the present invention may include one or more of the following features: a particle source; a dispensing device configured to receive source material from the particle source, wherein the dispensing device comprises a plurality of nozzle structures; nozzle structures that each include at least one opening defined along a center axis of the nozzle structure and terminating at a dispensing end thereof; nozzle structures that are separated from other adjacent nozzle structures by at least an internozzle distance (L) defined by the distance between center axes of nozzle structures, wherein the ratio of the internozzle distance (L) to a diameter (D) of the opening at the dispensing end is equal to or greater than 2; an electrode isolated from the dispensing end, wherein a nonuniform electrical field is created between the dispensing ends and the electrode such that a spray of particles having an electrical charge applied thereto is dispensed from the dispensing end of each nozzle structure; nozzle structures that include a capillary tube that has a body portion and a tapered capillary tip at the dispensing end of the capillary tube; nozzle structures that include a tapered portion used to form the opening at the dispensing end, wherein at least a part of each of the nozzle structures extend from an integral multiple nozzle structure conductive portion; nozzle structures that include a solid post along a center axis extending through the opening at the dispensing end thereof; dispensing ends of the nozzle structures that are positioned in an x-y plane and have the center axis thereof aligned along the z axis; a circular configuration of nozzle structures including an outer multiple nozzle structure ring and one or more inner multiple nozzle structure rings, wherein each of the outer multiple nozzle structure ring and the inner multiple nozzle structure rings are concentric about a center nozzle structure; a circular configuration of nozzle structures, wherein each of the nozzle structures of the one or more inner multiple nozzle structure rings are at a substantially equal internozzle distance (L) from adjacent nozzle structures; one or more separation structures positioned between nozzle structures and configured such that cone jets are allowed to form at the dispensing end of each nozzle structure; nozzle structures that include at least a first and second opening terminating at the dispensing end of each nozzle structure; a first particle source of at least a first fluid composition including an active ingredient to be dispensed through the first opening and a second particle source of at least a second fluid composition including a coating component to be dispensed through the second opening so as to provide sprays of coated active ingredients; an excipient material provided on a target surface positioned such that the sprays of particles are directed for contact with the excipient material; and a charged pattern positioned such that the sprays of particles is directed for contact with the charged pattern; a container operable by a user for inhalation of contents therein positioned such that the sprays of particles are directed therein.
The above summary of the present invention is not intended to describe each embodiment or every implementation of the present invention. Advantages, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings.